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Diabetic retinopathy (DR) is a secondary complication of diabetes that can lead to visual impairment and blindness. The retinal pigment epithelium (RPE) is a monolayer of pigment cells that forms the blood–retinal barrier (BRB) via tight junction (TJ) proteins and plays a crucial role in the physiological function of the retina. Hyperglycemia induces RPE death and BRB breakdown, which accelerates the process of DR. Curcumin, an active extract of Curcuma longa, has anti-inflammatory, antioxidant, antiapoptotic, and neuroprotective properties. However, the effect of Curcumin on the BRB under high glucose conditions remains unknown. This study aimed to investigate the protective effects of Curcumin on RPE physiology in vitro and in vivo. Curcumin significantly alleviated cell viability inhibition under high glucose conditions. Moreover, high glucose reduced extracellular signal-regulated kinase and Akt pathways activation to diminish RPE cell growth but reversed by Curcumin treatment. Curcumin protected not only TJ integrity but also retinoid regeneration through TJ proteins and isomerase modulation in diabetic retina. Furthermore, Curcumin decreased the expression of angiogenic factor to inhibit retinal neovascularization. Finally, Curcumin treatment markedly reduced apoptosis during hyperglycemia. In conclusion, Curcumin can alleviate the progression of DR by promoting RPE survival, TJ integrity, retinoid isomerase activity, RPE senescence inhibition, and neovascularization. Therefore, Curcumin exhibits high potential for use as a therapeutic agent for early DR.

Background Both high and low levels of serum potassium measurements are linked with a higher risk of adverse clinical events among patients with type 2 diabetes. The study was aimed at evaluating the implications of the various degrees of initial estimated glomerular filtration rate (eGFR) change on subsequent serum potassium homeostasis following sodium–glucose cotransporter‐2 inhibitor (SGLT2i) initiation among patients with type 2 diabetes. Methods and Results We used medical data from a multicenter health care provider in Taiwan and recruited 5529 patients with type 2 diabetes with baseline/follow‐up eGFR data available after 4 to 12 weeks of SGLT2i treatment from June 1, 2016, to December 31, 2018. SGLT2i treatment was associated with an initial mean (SEM) eGFR decline of −3.5 (0.2) mL/min per 1.73 m2 in overall study participants. A total of 36.7% (n=2028) of patients experienced no eGFR decline, and 57.9% (n=3201) and 5.4% (n=300) of patients experienced an eGFR decline of 0% to 30% and >30%, respectively. Patients with an initial eGFR decline of >30% were associated with higher variability in consequent serum potassium measurement when compared with those without an initial eGFR decline. Participants with a pronounced eGFR decline of >30% were associated with a higher risk of hyperkalemia ≥5.5 (adjusted hazard ratio,4.59 [95% CI, 2.28–9.26]) or use of potassium binder (adjusted hazard ratio, 2.65 [95% CI, 1.78–3.95]) as well as hypokalemia events

Glaucoma is considered a neurodegenerative disease characterized by progressive visual field defects that may lead to blindness. Although controlling intraocular pressure (IOP) is the mainstay of glaucoma treatment, some glaucoma patients have unmet needs due to unclear pathogenic mechanisms. Recently, there has been growing evidence that neuroinflammation is a potential target for the development of novel antiglaucoma agents. In this study, we investigated the protective effects and cellular mechanisms of H7E, a novel small molecule inhibits HDAC8, using in vitro and in vivo glaucoma-like models. Importantly, H7E mitigated extracellular MMP-9 activity and MCP-1 levels in glutamate- or S100B-stimulated reactive Müller glia. In addition, H7E inhibited the upregulation of inflammation- and proliferation-related signaling pathways, particularly the ERK and JNK MAPK pathways. Under conditions of oxidative damage, H7E prevents retinal cell death and reduces extracellular glutamate released from stressed Müller glia. In a mouse model of NMDA-induced retinal degeneration, H7E alleviated functional and structural defects within the inner retina as assessed by electroretinography and optical coherence tomography. Our results demonstrated that the newly identified compound H7E protects against glaucoma damage by specifically targeting HDAC8 activity in the retina. This protective effect is attributed to the inhibition of Müller glial activation and the prevention of retinal cell death caused by oxidative stress.

BackgroundPrevious studies have shown that global constructive work (CW) and wasted work (WW) predict response to cardiac resynchronization therapy (CRT). This study evaluated the predictive value of regional CW and WW for reverse remodeling and clinical outcomes after CRT.MethodsWe performed a prospective study involving 134 CRT candidates with left bundle branch block and left ventricular ejection fraction ≤35%. Global and regional CW and WW were calculated using pressure-strain loop analysis. CRT response was defined by reverse remodeling as a reduction of ≥15% in left ventricular end-systolic volume after six months.ResultsAt six-month follow-up, 92 (69%) patients responded to CRT. Of the regional CW and WW measures, lateral wall (LW) CW and septal WW were most strongly and significantly correlated with reverse remodeling. At multivariate analysis, LW CW and septal WW were both independent determinants of reverse remodeling. When LW CW and septal WW were included in the model, global CW and WW were not independently associated with reverse remodeling. LW CW and septal WW predicted reverse remodeling with an area under the curve (AUC) of 0.783 (95% CI: 0.700–0.866) and 0.737 (95% CI: 0.644–0.831), respectively. Using both variables increased the AUC to 0.832 (95% CI: 0.755–0.908). Both LW CW ≤878 mmHg% (HR 2.01; 95% CI: 1.07–3.79) and septal WW ≤181 mmHg% (HR 2.60; 95% CI: 1.38–4.90) were significant predictors of combined death and HF hospitalization at two-year follow-up.ConclusionLW CW and septal WW before CRT are important determinants of reverse remodeling and clinical outcomes.

Background and Objectives: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case–control study, we used Taiwan’s nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods: All data were retrospectively obtained from Taiwan’s National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results: Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage (p < 0.0001) and lower all-cause mortality rates (p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions: Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and leukoencephalopathy (CADASIL) is the most frequent genetic cerebrovascular disease. The clinical aspects of the disease in relation to the various types of lesions on Magnetic Resonance Imaging (MRI) vary widely within families but also between multiple cohorts reported worldwide. Many limitations prevent the comparison of imaging data obtained using different scanners and sequences, in different patients cohorts. We aimed to develop and validate a practical tool to inventory quickly the most important MRI features in CADASIL for comparing imaging data across different populations. Methods: The Inventory Tool (CADA-MRIT) was designed by consensus after repeated expert meetings. It consisted of eleven imaging items for evaluating periventricular, deep, and superficial white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMB), centrum semiovale and basal ganglia dilated perivascular spaces (PVS), superficial and deep atrophy, large infarcts, and macrobleeds. The reliability, clinical relevance and time-effectiveness of the CADA-MRIT were assessed using data from three independent cohorts of patients. Results: Imaging data from 671 CADASIL patients (440 from France, 119 from Germany and 112 from Taiwan) were analyzed. Their mean age was 53.4 ± 12.2 years, 54.5% were women, 56.2% had stroke, and 31.1% had migraine with aura. Any lacune was present in at least 70% of individuals, while CMB were present in 83% of patients from the Asian cohort and in only 35% European patients. The CADA-MRIT scores obtained for WMH, CMB and PVS were comparable regardless of the scanner or sequence used (weighted κ > 0.60). Intrarater and interrater agreements were good to very good (weighted κ > 0.60). Global WMH and atrophy scores strongly correlated with the exact volumetric quantification of WMH or brain parenchymal fraction (Pearson r > 0.60). Different imaging scores were significantly associated with the main clinical manifestations of the disease. The time for evaluating one patient was around 2-3 minutes. Discussion: The CADA-MRIT is an easy-to-use instrument for analyzing and comparing the most frequent MRI lesions of CADASIL across different populations. This tool is reliable. It can be used with different imaging sequences or scanners.

Abstract Blue light is part of the natural light spectrum that emits high energy. Currently, people are frequently exposed to blue light from 3C devices, resulting in a growing incidence of retinopathy. The retinal vasculature is complex, and retinal vessels not only serve the metabolic needs of the retinal sublayers, but also maintain electrolyte homeostasis by forming the inner blood-retinal barrier (iBRB). The iBRB, which is primarily composed of endothelial cells, has well-developed tight junctions. However, with exposure to blue light, the risks of targeting retinal endothelial cells are currently unknown. We found that endothelial claudin-5 (CLDN5) was rapidly degraded under blue light, coinciding with the activation of a disintegrin and metalloprotease 17 (ADAM17), even at non-cytotoxic lighting. An apparently broken tight junction and a permeable paracellular cleft were observed. Mice exposed to blue light displayed iBRB leakage, conferring attenuation of the electroretinogram b-wave and oscillatory potentials. Both pharmacological and genetic inhibition of ADAM17 remarkably alleviated CLDN5 degradation induced by blue light. Under untreated condition, ADAM17 is sequestered by GNAZ (a circadian-responsive, retina-enriched inhibitory G protein), whereas ADAM17 escapes from GNAZ by blue light illuminance. GNAZ knockdown led to ADAM17 hyperactivation, CLDN5 downregulation, and paracellular permeability in vitro, and retinal damage mimicked blue light exposure in vivo. These data demonstrate that blue light exposure might impair the iBRB by accelerating CLDN5 degradation through the disturbance of the GNAZ-ADAM17 axis.

Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most prevalent monogenic cerebral small‐vessel disease. Phenotype variability in CADASIL suggests the possible role of genetic modifiers. We aimed to investigate the contributions of the APOE genotype and Neurogenic locus notch homolog protein 3 (NOTCH3) variant position to cognitive impairment associated with CADASIL. Methods and Results Patients with the cysteine‐altering NOTCH3 variant were enrolled in a cross‐sectional study, including the Mini‐Mental State Examination (MMSE), brain magnetic resonance imaging, and APOE genotyping. Cognitive impairment was defined as an MMSE score

Glioblastoma (GBM) stands as the most prevalent primary malignant brain tumor, typically resulting in a median survival period of approximately thirteen to fifteen months after undergoing surgery, chemotherapy, and radiotherapy. Nucleobindin-2 (NUCB2) is a protein involved in appetite regulation and energy homeostasis. In this study, we assessed the impact of NUCB2 expression on tumor progression and prognosis of GBM. We further evaluated the relationship between NUCB2 expression and the sensitivity to chemotherapy and radiotherapy in GBM cells. Additionally, we compared the survival of mice intracranially implanted with GBM cells. High NUCB2 expression was associated with poor prognosis in patients with GBM. Knockdown of NUCB2 reduced cell viability, migration ability, and invasion ability of GBM cells. Overexpression of NUCB2 resulted in reduced apoptosis following temozolomide treatment and increased levels of DNA damage repair proteins after radiotherapy. Furthermore, mice intracranially implanted with NUCB2 knockdown GBM cells exhibited longer survival compared to the control group. NUCB2 may serve as a prognostic biomarker for poor outcomes in patients with GBM. Additionally, NUCB2 not only contributes to tumor progression but also influences the sensitivity of GBM cells to chemotherapy and radiotherapy. Therefore, targeting NUCB2 protein expression may represent a novel therapeutic approach for the treatment of GBM.

Age-related macular degeneration (AMD) is the leading cause of low vision and blindness for which there is currently no cure. Increased matrix metalloproteinase-9 (MMP-9) was found in AMD and potently contributes to its pathogenesis. Resident microglia also promote the processes of chronic neuroinflammation, accelerating the progression of AMD. The present study investigates the effects and mechanisms of the natural compound theissenolactone B (LB53), isolated from Theissenia cinerea, on the effects of RPE dysregulation and microglia hyperactivation and its retinal protective ability in a sodium iodate (NaIO3)-induced retinal degeneration model of AMD. The fungal component LB53 significantly reduces MMP-9 gelatinolysis in TNF-α-stimulated human RPE cells (ARPE-19). Similarly, LB53 abolishes MMP-9 protein and mRNA expression in ARPE-19 cells. Moreover, LB53 efficiently suppresses nitric oxide (NO) production, iNOS expression, and intracellular ROS levels in LPS-stimulated TLR 4-activated microglial BV-2 cells. According to signaling studies, LB53 specifically targets canonical NF-κB signaling in both ARPE-19 and BV-2 microglia. In an RPE-BV-2 interaction assay, LB53 ameliorates LPS-activated BV-2 conditioned medium-induced MMP-9 activation and expression in the RPE. In NaIO3-induced AMD mouse model, LB53 restores photoreceptor and bipolar cell dysfunction as assessed by electroretinography (ERG). Additionally, LB53 prevents retinal thinning, primarily the photoreceptor, and reduces retinal blood flow from NaIO3 damage evaluated by optic coherence tomography (OCT) and laser speckle flowgraphy (LSFG), respectively. Our results demonstrate that LB53 exerts neuroprotection in a mouse model of AMD, which can be attributed to its anti-retinal inflammatory effects by impeding RPE-mediated MMP-9 activation and anti-microglia.

Abstract The atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) was classified as a new tumor by the World Health Organization (WHO) in 2020. The tumor is benign and commonly occurs in the limbs. Paraspinal presentations are rare. A 38‐year‐old man presented at our clinic complaining of sudden onset back pain. No neurological deficit was found. The magnetic resonance imaging (MRI) revealed a well‐defined heterogeneous mass in the left psoas muscle, from L1 to L3 extending over the L1 and L2 neuroforamen. The tumor was totally excised. Pathology led to an ASPLT diagnosis. Clinical symptoms improved and there was no postsurgical neurological deficit. This case of ASPLT, located in an uncommon location and present an unusual cluster of symptoms, could be treated by surgical excision, usually the first‐treatment strategy. Totally, removal was achieved because there was a clear morphological margin. The risk of metastatic dissemination was minimal, though there remains a nonnegligible risk of local recurrence.

It is convenient to have advances in science and technology so that people obtain information without going out. We explore the intention of the use of housing apps based on the unified theory of acceptance and the use of technology. A total of 365 questionnaires were collected with 8 incomplete answers discarded. The snowball sampling method was used for confirmatory factor analysis and SEM structural equation model analysis. The research results show the following. (1) Housing app users can quickly obtain knowledge and information about houses, and it is more convenient. (2) Both effort expectancy and social influence have a direct and positive effect on behavior intention when using the housing app. (3) There is no significant impact after adding moderator variables of gender, age, and income in Unified Theory of Acceptance and Use of Technology, (UTAUT). It is convenient and helpful to use the housing app. Therefore, the use of the housing app will be an indispensable trend.

Abstract Background Depending on their distinct properties, titanium dioxide nanoparticles (TiO2-NPs) are manufactured extensively and widely present in our daily necessities, with growing environmental release and public concerns. In sunscreen formulations, supplementation of TiO2-NPs may reach up to 25% (w/w). Ocular contact with TiO2-NPs may occur accidentally in certain cases, allowing undesirable risks to human vision. This study aimed to understand the barrier integrity of retinal endothelial cells in response to TiO2-NP exposure. bEnd.3 cells and human retinal endothelial cells (HRECs) were exposed to TiO2-NP, followed by examination of their tight junction components and functions. Results TiO2-NP treatment apparently induced a broken structure of the junctional plaques, conferring decreased transendothelial electrical resistance, a permeable paracellular cleft, and improved cell migration in vitro. This might involve rapid activation of metalloproteinase, a disintegrin and metalloproteinase 17 (ADAM17), and ADAM17-mediated claudin-5 degradation. For the in vivo study, C57BL/6 mice were administered a single dose of TiO2-NP intravitreally and then subjected to a complete ophthalmology examination. Fluorescein leakage and reduced blood flow at the optical disc indicated a damaged inner blood-retinal barrier induced by TiO2-NPs. Inappreciable change in the thickness of retinal sublayers and alleviated electroretinography amplitude were observed in the TiO2-NP-treated eyes. Conclusions Overall, our data demonstrate that TiO2-NP can damage endothelial cell function, thereby affecting retinal electrophysiology.

Abstract Objective To develop an easily applicable screening score to guide NOTCH3 p.R544C genetic testing for patients who presented with acute ischemic cerebrovascular events in Taiwan. Methods 1734 patients who presented with ischemic cerebrovascular events were enrolled from the Formosa Stroke Genetic Consortium stroke registry and were screened for the NOTCH3 p.R544C mutation. Clinical and MRI characteristics of NOTCH3 p.R544C mutation carriers (n = 36) and a subset of noncarriers (n = 673) were tested in a logistic regression model to identify key features associated with the NOTCH3 p.R544C carrier status. Variables and their odds ratios in the regression model were used to develop the R544C screening score to predict positive NOTCH3 p.R544C test results. Results We constructed the R544C screening score using five clinical and imaging characteristics, including stroke onset before 50 years of age, the small vessel occlusion subtype, a family history of stroke/TIA in siblings, external capsule involvement, and advanced deep white matter hyperintensity. The area under the ROC curve of the screening score was 0.867 (95% CI = 0.810‐0.924). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 0.75, 0.88, 0.13, 0.99, and 0.88, respectively, for a cutoff score of 5 points. In addition, the R544C screening score was validated in another cohort composed of 235 stroke patients with comparable performance (area under the ROC curve = 0.957, 95% CI = 0.916‐0.997). Interpretations For Taiwanese patients presenting with acute ischemic cerebrovascular events, the R544C screening score is easily applicable and can efficiently select high‐risk patients for NOTCH3 p.R544C mutation test.

Abstract Background Optimization of vascular risk factor control is emerging as an alternative approach to improve cognitive outcomes in Alzheimer’s disease, although its efficacy is still under debate. We aimed to investigate the contribution of vascular risk factors on Alzheimer’s biomarkers and conversion rate to dementia in subjects with mild cognitive impairment (MCI) with low cerebral small vessel disease burden. Methods Two hundred ninety-five newly diagnosed MCI subjects were enrolled from March 2005 to May 2017 for a cross-sectional assessment of vascular risk factors and Alzheimer’s plasma and imaging biomarkers, followed by a cognitive outcome assessment 24 months after enrollment. The association between vascular risk factors and Alzheimer’s biomarkers were tested using multivariable linear regression models adjusted with age, gender, education, and APOE ε4 allele. The association between vascular risk factors and conversion to dementia was tested using multivariable logistic regression models adjusted with age, gender, education, and baseline Mini-Mental State Examination (MMSE) score. Results At baseline, higher low-density lipoprotein (LDL) cholesterol level was associated with more advanced plasma biomarkers, including Aβ42/Aβ40 ratio (P = 0.012) and tau level (P = 0.001). A history of hypertension was associated with more advanced white matter hyperintensity (P = 0.011), while statin therapy for dyslipidemia was associated with less advanced white matter hyperintensity (P = 0.002). At 24 months, individual vascular risk factor was not significantly associated with cognitive outcome. By contrast, statin therapy for dyslipidemia was associated with reduced conversion to dementia (adjusted OR = 0.191, 95% CI = 0.062~0.586, P = 0.004). Conclusions For MCI subjects, dyslipidemia may contribute to AD-related neurodegeneration while hypertension may contribute to vascular pathology. The association between statin therapy for dyslipidemia and reduced conversion to dementia supports further interventional study to evaluate the potential beneficial effect of statin in MCI subjects.

Abstract Background Stroke remains the most cumbersome disease burden in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). This study aimed to investigate whether plasma biomarkers can reflect disease severity and predict stroke recurrence in CADASIL patients. Methods Sixty-three CADASIL patients (mean age 58.9 ± 9.3 years old, male 63%) from a multicenter registry and 17 controls were recruited. Plasma biomarkers, namely neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1), were measured using an ultra-sensitive single molecule array at baseline. Neuroimaging markers assessed included the Fazekas scale of white matter hyperintensity, numbers of lacunes, and cerebral microbleeds (CMBs). Cox proportional hazards regression models were applied to calculate the hazard ratio (HR) of plasma biomarkers at baseline for predicting incident stroke during follow-up. Results Plasma NfL, GFAP, and UCHL1 levels were significantly elevated in the CADASIL patients than in the controls. Among the CADASIL patients, both plasma NfL and GFAP levels positively correlated with the numbers of CMBs (r = 0.32 and r = 0.37, respectively; both p < 0.05). Higher plasma levels of NfL and GFAP were associated with any stroke (odds ratio 2.02, 95% confidence interval [CI] 1.06–3.87) and ICH (odds ratio 2.06, 95% CI 1.26–3.35) at baseline, respectively. Within a mean follow-up period of 3.1 ± 2.1 years, 10 patients (16%) had incident stroke and 6 of them were ICH. Higher baseline NfL (HR 1.93, 95% CI 1.19–3.13) predicted any incident stroke, whereas higher GFAP (HR 2.80, 95% CI 1.21–6.53) predicted incident ICH. Conclusions In CADASIL patients, plasma NfL can be a promising biomarker for monitoring incident stroke, whereas GFAP may have a role in cerebral hemorrhage.

BackgroundCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in NOTCH3, is the most common cause of hereditary cerebral small vessel disease. Whether it will involve systemic vasculopathy such as retinal vessel remains unknown. Optical coherence tomography angiography (OCT-A) is a noninvasive technique for visualising retinal blood flow. We analysed vessel density and retinal thickness in patients with CADASIL and investigated their correlations with disease severity.MethodsThis prospective study enrolled 35 patients with CADASIL (59 eyes) and 35 healthy controls (54 eyes). OCT-A was used to measure the vessel density of the macular region and the thickness of retinal layers. Patients with CADASIL were divided into stroke (n = 20) and nonstroke (n = 15) subgroups and underwent cognition and gait speed evaluation. Neuroimaging markers of cortical thickness, white matter hyperintensity, lacunae, and cerebral microbleeds were examined through brain magnetic resonance imaging.ResultsThe OCT-A parameters, including vessel density, were comparable between the patients with CADASIL and the controls. In patients with CADASIL, vessel density in the superficial retinal plexus in the macula as was inner retinal thickness was significantly lower in the stroke than the nonstroke subgroup. Macular vessel density and inner retinal thickness were positively correlated with gait speed, while negatively correlated with number of lacunae.ConclusionsOCT-A is potentially a useful tool for evaluating disease severity, ischaemic burden, and neurodegeneration in patients with advanced CADASIL.

Supercritical carbon dioxide dyeing (SDD) as a dyeing media not only provides a friendly dyeing environment but also significantly increases polymeric dyeing performances ascribed to strong azo dye affinity. Disperse azo dyes have shown to be highly efficient dyeing agents due to their facile coupling synthesis, side chains position, and length tunability to optimize absorption properties. Herein, we first synthesize two series of disperse red azo dyes via a coupling chemical route. Further, we investigate the position of the electron withdrawing group and alkyl chains length impact onto the absorption and color fastness properties. Upon synthesis, 1H NMR and mass spectroscopy were used to characterize our newly synthesized series dye structure. Also, according to spectroscopic characterization, the functional group positions as well as the alkyl chains length have a major impact on the dye series maximum light absorption wavelength and performance. We have performed SDD dyeing of polyethylene terephthalate woven and determined each dye color fastness, we find that a reduced electron withdrawing effect and alkyl chains increase reduce color-fastness performances. Overall, our dyes exhibited a good resistance against detergent water, perspiration, abrasion, and friction.

Abstract Background Gold nanoparticles (Au-NPs) have extensive applications in electronics and biomedicine, resulting in increased exposure and prompting safety concerns for human health. After absorption, nanoparticles enter circulation and effect endothelial cells. We previously showed that exposure to Au-NPs (40–50 nm) collapsed endothelial tight junctions and increased their paracellular permeability. Inhaled nanoparticles have gained significant attention due to their biodistribution in the brain; however, little is known regarding their role in cerebral edema. The present study investigated the expression of aquaporin 1 (AQP1) in the cerebral endothelial cell line, bEnd.3, stimulated by Au-NPs. Results We found that treatment with Au-NPs induced AQP1 expression and increased endothelial permeability to water. Au-NP exposure rapidly boosted the phosphorylation levels of focal adhesion kinase (FAK) and AKT, increased the accumulation of caveolin 1 (Cav1), and reduced the activity of extracellular regulated protein kinases (ERK). The inhibition of AKT (GDC-0068) or FAK (PF-573228) not only rescued ERK activity but also prevented AQP1 induction, whereas Au-NP-mediated Cav1 accumulation remained unaltered. Neither these signaling molecules nor AQP1 expression responded to Au-NPs while Cav1 was silenced. Inhibition of ERK activity (U0126) remarkably enhanced Cav1 and AQP1 expression in bEnd.3 cells. These data demonstrate that Au-NP-mediated AQP1 induction is Cav1 dependent, but requires the repression on ERK activity. Mice receiving intranasally administered Au-NPs displayed cerebral edema, significantly augmented AQP1 protein levels; furthermore, mild focal lesions were observed in the cerebral parenchyma. Conclusions These data suggest that the subacute exposure of nanoparticles might induce cerebral edema, involving the Cav1 dependent accumulation on endothelial AQP1.

Supercritical carbon dioxide dyeing (SCDD) not only enables strong dyeing performance for a versatile range of polymer material but is also regarded as a green chemical media due to its low environmental impact as well as low risk of product denaturation. Over the decades, azo disperse dyes have been revealed to be efficient dyes and represent the wide majority of dyeing material. Azo dyes possess a wide variety of functional groups to optimize dye synthesis and tune the light absorption properties. Using SCDD, end-chain of different lengths, and functional group exhibiting various electronic affinity, six disperse red azo dyes were synthesized to investigate dyeing performances as woven fabric type, color strain, and color fastness after dyeing are discussed. Dye structure synthesized through a coupling reaction was confirmed by 1H NMR and mass spectroscopy. We found that the light absorption wavelength and absorption coefficient value variation are associated to the nature of the functional group. From the color strength values of the polyethylene terephthalate woven after dyeing, we find that the fiber host and dye dopant chemical structure greatly influence the dyeing process by providing enhanced woven, color strain, and color fastness. In comparison with commercial products, our approach not only improves the dyeing process but also guarantees a strong resistance of the dyed product against water, detergent, perspiration, abrasion, and friction.

Background/Aims: Blue light-emitting diode light (BLL)-induced phototoxicity plays an important role in ocular diseases and causes retinal degeneration and apoptosis in human retinal pigment epithelial (RPE) cells. Cistanche tubulosa extract (CTE) is a traditional Chinese medicine with many beneficial protective properties; however, few studies have examined the ocular protective roles of CTE. In this study, we investigated the mechanisms underlying the effects of CTE on BLL-induced apoptosis in vitro and in vivo. Methods: RPE cells were applied in the current in vitro study and cell viability was determined by an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptosis-related protein expression was determined by western blot analysis and immunofluorescence staining. Brown Norway rats were used to examine exposure to commercially available BLL in vivo. Hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot assays were used to examine retinal morphological deformation. Results: CTE significantly inhibited hydrogen peroxide-, tert-butyl hydroperoxide-, sodium azide-, and BLL-induced RPE damage. Further, CTE reduced the expression of apoptotic markers such as cleaved caspase-3 and TUNEL staining after BLL exposure by inactivating apoptotic pathways, as shown via immunofluorescent staining. In addition, CTE inhibited the BLL-induced phosphorylation of c-Jun N-terminal kinase, extra signal-related kinases 1/2, and p38 in RPE cells. In vivo, the oral administration of CTE rescued 60-day periodic BLL exposure-induced decrements in retinal thickness and reduced the number of TUNEL-positive cells in the brown Norway rat model. Conclusion: CTE is a potential prophylactic agent against BLL-induced phototoxicity.

Age-related macular degeneration (AMD) occurs due to an abnormality of retinal pigment epithelium (RPE) cells that leads to gradual degeneration of the macula. Currently, AMD drug pipelines are endowed with limited options, and anti-VEGF agents stand as the dominantly employed therapy. Despite the proven efficacy of such agents, the evidenced side effects associated with their use underscore the need to elucidate other mechanisms involved and identify additional molecular targets for the sake of therapy improvement. The previous literature provided us with a solid rationale to preliminarily explore the potential of selective HDAC6 and HSP90 inhibitors to treat wet AMD. Rather than furnishing single-target agents (either HDAC6 or HSP90 inhibitor), this study recruited scaffolds endowed with the ability to concomitantly modulate both targets (HDAC6 and HSP90) for exploration. This plan was anticipated to accomplish the important goal of extracting amplified benefits via dual inhibition (HDAC6/HSP90) in wet AMD. As a result, G570 (indoline-based hydroxamate), a dual selective HDAC6-HSP90 inhibitor exerting its effects at micromolar concentrations, was pinpointed in the present endeavor to attenuate blue light-induced cell migration and retinal neovascularization by inhibiting VEGF production. In addition to the identification of a potential chemical tool (G570), the outcome of this study validates the candidate HDAC6-HSP90 as a compelling target for the development of futuristic therapeutics for wet AMD.

Background: Granuloma annulare (GA) is a benign, usually self-limited, inflammatory skin disease. Although there have been several studies that review pathoclinical features about GA, the relevant epidemiological study in Taiwan was lacking. The purpose of this study is to evaluate the pathoclinical features and treatment outcome of GA in Taiwan. Methods: This study was performed by retrospective review of medical records and pathological slides of the patients diagnosed as GA in a tertiary referral medical center in Taiwan. Fisher exact test was performed to compare remission rate between adults and children, treatment and nontreatment groups. Result: The study included 44 patients with GA: 23 male and 21 female. The incidence of GA showed a bimodal age distribution (peaks below 20 years and above 50 years). Localized type is most common, followed by generalized variant. Perforating GA is the rarest subtype and was exclusively found in children. The pathology of GA is characterized by necrobiosis (100%), palisading granuloma (81.8%), and mucin deposition (93.2%); 13.6% and 6.8% of GA patients had history of diabetes mellitus and dyslipidemia, respectively. Conclusion: In contrast to the reported studies, the incidence of GA showed a bimodal age incidence with slight male preponderance. Our patients had higher prevalence of diabetes mellitus than the general Taiwanese population but had no increase in incidence of dyslipidemia. Whether patients received treatment or not does not affect the disease outcome. Overall, children have better prognosis than adults.

The aim of this study was to investigate the effects of a natural component, theissenolactone C (LC53), on the ocular inflammation of experimental endotoxin-induced uveitis (EIU) and its related mechanisms in microglia. Evaluation of the severity of anterior uveitis indicated that LC53 treatment significantly decreased iridal hyperemia and restored the clinical scores. Additionally, the deficient retina functions of electroretinography were improved by LC53. LC53 significantly reduced levels of tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1, protein leakage and activation of matrix metalloproteinases in the anterior section during EIU. Moreover, LC53 treatment decreased the oxidative stress as well as neuroinflammatory reactivities of GFAP and Iba-1 in the posterior section. Furthermore, LC53 decreased the phosphorylation of p65, expression of HSP90, Bax, and cleaved-caspase-3 in EIU. According to the microglia studies, LC53 significantly abrogated the productions of TNF-α, PGE2, NO and ROS, as well as inducible NO synthase and cyclooxygenase-2 expression in LPS-stimulated microglial BV2 cells. The microglial activation of IKKβ, p65 phosphorylation and nuclear phosphorylated p65 translocation were strongly attenuated by LC53. On the other hand, LC53 exhibited the inhibitory effects on JNK and ERK MAPKs activation. Our findings indicated that LC53 exerted the ocular-protective effect through its inhibition on neuroinflammation, glial activation, and apoptosis in EIU, suggesting a therapeutic potential with down-regulation of the NF-κB signaling for uveitis and retinal inflammatory diseases.

It was highlighted that the original article [1] contained the wrong Fig. 1.

Background: Inflamed epidermal cysts are common clinical conditions, and they frequently form abscesses. We designed a study to delineate the bacteriology of inflamed epidermal cysts. Methods: We enrolled 61 adult patients with inflamed epidermal cysts characterized by surface erythema, with or without tenderness, or localized abscess formation within the cyst cavity. Incision and drainage of the cysts were performed, and the contents were sent for aerobic and anaerobic bacterial culture. The locations of the cyst and culture results were recorded for statistical analysis. Results: A total of 61 cysts and 122 cultures were obtained. The most common locations of the inflamed cysts were the face, neck, and scalp (34.4%), followed by the trunk (32.8%), then the buttocks, inguinal areas, perineum, and axillae (16.4%), and the extremities (16.4%). The culture results were positive in 88.5% of patients, and anaerobes were more frequently isolated than were aerobes. Pure aerobes represented 31.1% of the cultures; pure anaerobes, 36.1%, and combined aerobes and anaerobes, 21.3% (n = 13). The most common anaerobic organisms found were Propionibacterium spp (40.8%), followed by Peptostreptococcus spp (36.7%), Staphylococcus saccharolyticus (14.4%), Prevotella (4.1%), Bacteroides fragilis (2.0%), and Fusobacterium spp (2.0%). The most commonly isolated aerobes were Staphylococcus spp (40%), followed by Enterobacter spp (11.3%), Proteus mirabilis (8.5%), Citrobacter diversus (8.5%), Klebsiella pneumoniae (5.7%), Corynebacterium (5.7%), Morganella morganii (2.9%), Enterococcus faecalis (2.9%), group A β-hemolytic streptococcus (2.9%), Pseudomonas aeruginosa (2.9%), and Providencia rettgeri (2.9%). Conclusions: Both aerobic and anaerobic microorganisms were present in the inflamed epidermal cysts, although the anaerobic bacteria, specifically, Propionibacterium spp and Peptostreptococcus spp, were isolated slightly more frequently. Antibiotics directed against anaerobes may be considered in the treatment regimen for inflamed epidermal cysts.

p53, can regulate cell apoptosis in both transcription-dependent and -independent manners. The transcription-independent pathway was demonstrated by the translocation of p53 to mitochondria. Our study showed that p53 mitochondrial translocation was found in mitomycin C (MMC)-treated HepG2. The p53 C-terminal domain is clustered with potential nuclear leading sequences and showed strong electrostatic ion-ion interactions with cardiolipin, phosphatidylglycerol and phosphatidic acid in vitro. Disruption of cardiolipin biosynthesis by phosphatidylglycero-phosphate synthase (PGS) or CDP-diacylglycerol synthase 2 (CDS-2) short hairpin RNA (shRNA) transfection eliminated the MMC-induced translocation of mitochondrial p53. The elimination of mitochondrial p53 translocation also reduced Bcl-xL and Bcl-2 mitochondrial distribution. In HEK 293T models with saturated p53 expression, the mitochondrial partition of p53, Bcl-xL, and Bcl-2 obviously decreased in their PGS shRNA- or CDS-2 shRNA-expressing stable clones. In p53-null H1299 models, both the mitochondrial partitions of Bcl-xL and Bcl-2 were strongly reduced in relation to the HEK 293T models. The Bcl-xL mitochondrial partition was elevated in H1299 models expressing pCEP4-p53wt suggesting the direct carrier role of p53 in transporting Bcl-xL to the mitochondria. We also found that the cytosolic pool of Bcl-xL and Bcl-2 remained unaffected in the low-dose MMC treatment but decreased in the high-dose MMC treatment. The cytosolic pool of Bcl-2 and Bcl-xL directly regulated their amounts in p53-dependent mitochondrial distribution. In the low-dose MMC treatment, the increased mitochondrial p53, Bcl-xL, and Bcl-2 could attenuate apoptosis. However, in the high-dose MMC treatment, only the p53 translocated to the mitochondria and resulted in apoptosis progression. On the basis of this study, we thought mitochondrial p53 might regulate apoptosis in a biphasic manner.

Skin diseases are common in children. Epidemiologic studies of skin diseases in schoolchildren performed by direct inspection by dermatologists are limited in Taiwan. The current study surveyed the prevalence of selected childhood dermatoses in Magong City, Penghu, the largest offshore island of Taiwan. Methods: A cross-sectional study was carried out in June 2005, in which a total of 3273 children aged 6−11 years living in Magong were examined by at least two board-certified dermatologists, with regard to the point prevalence of acne, ephelides, atopic dermatitis, warts, keloids, vitiligo, fungal infections, alopecia areata and psoriasis. The skin of the scalp, face, neck, trunk and extremities were inspected; that of the breast, genitalia and feet were skipped for privacy. Results: Acne vulgaris was found at the age of 7 in both genders, with comedones being the earliest manifestation. The overall prevalence of acne was 17.3% (95% CI, 16−18.6%). Ephelides were frequently observed in the children (prevalence rate, 15.24%; 95% CI, 14−16.47%). The prevalence of atopic dermatitis was 4.33% (95% CI, 3.63−5.03%), with more boys affected than girls (1.49:1) (p = 0.03). The prevalence of warts on the hands was 2.81% (95% CI, 2.24−3.38%). Keloids were identified in seven boys and four girls, accounting for 0.33% of the children (95% CI, 0.13−0.53%). Three children had vitiligo (prevalence rate, 0.09%; 95% CI, 0−0.19%). The prevalence of fungal infection including tinea nigra, tinea versicolor and tinea corporis was 0.24% (95% CI, 0.07−0.41%). Neither alopecia areata nor psoriasis was identified. Conclusion: Compared with our previous study in Kaohsiung County using similar methodology, the point prevalence of atopic dermatitis and ephelides was significantly higher whereas that of fungal infection was lower in Penghu. Unexpectedly, tinea nigra was not rare in Penghu.

A contact coating method is developed to cover the nano-channels with 100 nm or 200 nm diameter and 400 nm depth with a poly(4-vinylphenol) (PVP). In such coating the nano-channels faces downwards and its vertical position is controlled by a motor. The surface is first lowered to be in immediate contact with the polyvinylpyrrolidone (PVPY) water solution with concentration from 1 to 5 wt%, then pulled at the speed of 0.004 to 0.4 mm/s. By tuning the pulling speed and concentration we can realize conformal, filled, top-only, as well as floating film morphology. For a reproducible liquid detachment from the solid, the sample has a small tilt angle of 3 degree. Contact coating is used to cover the Al grid base of the vertical space-charge-limited transistor with PVPY. Poly(3-hexylthiophene-2,5-diyl) (P3HT) as the semiconductor. The transistor breakdown voltage is raised due to base coverage achieved by contact coating.

Background and purpose NOTCH3 p.R544C mutation accounts for 5% of spontaneous intracerebral haemorrhage (ICH) in East Asian patients. We investigated whether certain CT features are associated with NOTCH3-related ICH.Methods Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation. The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation, including burden of white matter lesion (WML), degree of brain atrophy, number of lacunes, prominent juxtacortical WML and prominent lobar lacunes, were analysed by neuroradiologists blinded to the mutation status.Results Of 299 patients with spontaneous ICH (mean age, 61 years; male, 68%; ICH volumes, 14.1±17.8 mL), 13 patients (4.3%) carried NOTCH3 p.R544C mutation. The clinical features, haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers. The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML (69.2% vs 17.8%, p

Developing an ideal luminescent material with exceptional performance in various aspects, such as affordability, low toxicity, high photostability and security, is vital for advanced optical anti-counterfeiting. Here, halogen-doping-dependent luminescence MoS2 quantum dots were synthesized via a simple hydrothermal method for optical anti-counterfeiting ink. The results show that F-, Cl- and Br- doping results in notable fluorescence blueshifts of MoS2 quantum dots and significant enhancements in the photoluminescence quantum yield (PLQY) of up to 5.7, 5.0, and 3.2 times, respectively. However, I- incorporation causes a fluorescence redshift and a 25% decrease of PLQY. This mechanism is elucidated using density functional theory (DFT) and experiments. Specifically, F-, Cl- and Br- doping localizes surface electrons and blocks sulfur vacancies in MoS2 quantum dots, enhancing the release of neutral excitons from trions and defect-bound excitons. Conversely, I- doping increases the surface charge and sulfur vacancies, favouring the conversion of neutral excitons into trions and defect-bound excitons. The halogen-doped MoS2 quantum dots are engineered as security ink, demonstrating high concealment, excellent photostability and easy fabrication. The study offers a novel way of tailoring fluorescence of MoS2 quantum dots, potentially extending to other transition metal dichalcogenide quantum dots and their optical anti-counterfeiting implementation. [ABSTRACT FROM AUTHOR]

Assuring e-learning quality is of interest worldwide. This paper introduces the methods of e-learning courseware quality assurance (a quality certification system) adopted by the eLQSC (e-Learning Quality Service Centre) in Taiwan. A sequential/explanatory design with a mixed methodology was used to gather research data and conduct data analyses. Sixty-seven e-learning courseware applications were evaluated using the e-Learning Courseware Quality Checklist (eLCQC). Analyses of item difficulty, item discrimination and generalizability indicated that the eLCQC provides high-quality evaluations. After participating in the certification process, the e-learning producers reported having more confidence in enhancing e-learning courseware quality. The certification experience also helped the producers to change their previous design concepts about e-learning courseware and to develop new concepts; further, their increased confidence about courseware design also enhanced their confidence in marketing courseware. (Contains 7 tables and 2 figures.)

Museums are one of the most important institutions providing students with the opportunity to gain knowledge, experience cultures, and develop different interests in an informal learning setting. As information and communication technology (ICT) has become more popular, many researchers have also become concerned with how to use mobile devices to support the museum's functions of lifelong learning. Although researchers have proposed several innovative types of mobile-device based electronic guidebooks, the effects of the most used audio-visual guidebooks have been rarely evaluated. This study explored the effect of a mobile electronic guidebook on visiting behaviors in a museum of history. Visitors' behaviors with two visiting modes (visiting with the electronic guidebook and visiting without supplementary tools) were compared. Forty-two college students were invited to visit the National Museum of History in Taiwan and were randomly assigned to one of the two visit modes. The results showed that the students with the electronic guidebook had a longer holding time with exhibits than the students without supplementary materials. The sequential analysis of visiting behaviors also showed that the students with the electronic guidebook displayed more inquisitive and structural behaviors when interacting with the exhibits. (Contains 6 figures and 5 tables.)